rs387906336
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_016006.6(ABHD5):c.46_47delAG(p.Arg16ValfsTer20) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,408,460 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ABHD5
NM_016006.6 frameshift, splice_region
NM_016006.6 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0570
Publications
1 publications found
Genes affected
ABHD5 (HGNC:21396): (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase) The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation. [provided by RefSeq, Jul 2008]
ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]
ANO10 Gene-Disease associations (from GenCC):
- autosomal recessive spinocerebellar ataxia 10Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 23 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-43691032-GGA-G is Pathogenic according to our data. Variant chr3-43691032-GGA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 5354.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016006.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ABHD5 | MANE Select | c.46_47delAG | p.Arg16ValfsTer20 | frameshift splice_region | Exon 1 of 7 | NP_057090.2 | |||
| ABHD5 | c.46_47delAG | p.Arg16ValfsTer20 | frameshift splice_region | Exon 1 of 8 | NP_001342115.1 | Q8WTS1 | |||
| ABHD5 | c.46_47delAG | p.Arg16ValfsTer20 | frameshift splice_region | Exon 1 of 6 | NP_001352579.1 | A0A2U3TZT9 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ABHD5 | MANE Select | c.35_36delAG | p.Thr13ValfsTer20 | frameshift | Exon 1 of 7 | ENSP00000495778.1 | Q8WTS1 | ||
| ABHD5 | TSL:1 | c.35_36delAG | p.Thr13ValfsTer20 | frameshift | Exon 1 of 6 | ENSP00000390849.3 | A0A2U3TZT9 | ||
| ABHD5 | c.35_36delAG | p.Thr13ValfsTer20 | frameshift | Exon 1 of 8 | ENSP00000637578.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000213 AC: 3AN: 1408460Hom.: 0 AF XY: 0.00000143 AC XY: 1AN XY: 700670 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1408460
Hom.:
AF XY:
AC XY:
1
AN XY:
700670
show subpopulations
African (AFR)
AF:
AC:
0
AN:
29072
American (AMR)
AF:
AC:
0
AN:
38594
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24560
East Asian (EAS)
AF:
AC:
0
AN:
33418
South Asian (SAS)
AF:
AC:
0
AN:
81168
European-Finnish (FIN)
AF:
AC:
0
AN:
50478
Middle Eastern (MID)
AF:
AC:
0
AN:
5612
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1087644
Other (OTH)
AF:
AC:
0
AN:
57914
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Triglyceride storage disease with ichthyosis (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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